Well, having actually seen multiple people shot with 45gr .223 now, I have some thoughts on the matter.
If you get that classic, B-21 pose, where you have a full frontal torso and the hands are at the side, then 45gr varmint loads have a lot of potential. They’ll make huge cavities with very shallow penetration; but because your average grown man is around 8-9” deep that’s not a problem.
However, if your average target is, say pointing a gun back at you, then his arms are typically extended right over his center mass. In that event, a 45gr varmint bullet that strikes an extended arm, is going to break that bone spectacularly and then the tiny remaining fragments will spray the chest and few will penetrate deeply enough you can’t pick them out with tweezers. Good news is that arm will be broken/smashed.
If for example, instead of extending a weapon towards you, the target does something insensible, like say turn away from you, you have the same problem - just with more meat, fat, and thicker bones intervening.
Or the target might be prone, or behind a car door, or a common household appliance, or any one of a dozen things that will dramatically reduce penetration on a small varmint bullet. But if you get that B21 shot, they are aces.